The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins that share sequence similarity with animal proteins having thrombospondin repeats. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or over express the disclosed polynucleotide sequences, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed polynucleotide sequences that can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, or cosmetic or nutriceutical applications.
Thrombospondins have been implicated in, inter alia, mediating angiogensis, cancer, and development. Proteins having thrombospondin repeats can act as receptors, secreted extracellular matrix proteins, and proteases.
The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins, and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with proteins having thrombospondin repeats.
The novel human nucleic acid sequences described herein, encode alternative proteins/open reading frames (ORFs) of 1,691, 446, 372, 724, 650, 845, 771, and 1,617 amino acids in length (see SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, and 16 respectively).
The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPs, or portions thereof that compete with native NHP, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and gene or regulatory sequence replacement constructs) or to enhance the expression of the described NHP polynucleotide sequences (e.g., expression constructs that place the described polynucleotide sequence under the control of a strong promoter system), and transgenic animals that express a NHP transgene, or xe2x80x9cknockoutsxe2x80x9d (which can be conditional) that do not express a functional NHP.
Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.
The Sequence Listing provides the sequences of the described NHP ORFs that encode the described NHP amino acid sequences. SEQ ID NO:17 describes a NHP ORF and flanking regions.